Antibiotic Resistance – the greatest threat to humanity? Brendan Borrell considers how exploration could help confront the major challenge of antibiotic resistance

The antibiotic era began with Alexander Fleming’s discovery of penicillin at St Mary’s Hospital in London in 1928. Fleming had witnessed first-hand the terrible effects of infectious disease while serving in the Royal Army Medical Corps in World War I, watching helplessly as wounded men died of sepsis – a reaction of the immune system to infection, damaging tissues and organs – and he became interested in developing a better treatment to replace the often ineffective antiseptics used at the time.

Fleming had been growing colonies of staphylococcus – a type of bacterium that is ubiquitous on human skin and can easily infect wounds – in Petri dishes, when he noticed an unexpected development. On one dish, which had been left open by mistake while Fleming was on holiday, there was a spot of green mould that was inhibiting the growth of the bacteria. Following some experimentation Fleming discovered that an extract from the mould, Penicillium notatum, was able to kill a wide variety of bacteria.

Chromatography being used to tackle antibiotic resistance
Over recent decades, molecular microbiology has unravelled the mechanisms of antibiotic resistance. Advanced chromatography techniques such as this have enabled scientists to understand the function of the various elements that compose a bacterium.

A decade later, a team of scientists based at Oxford University managed to isolate the active ingredient of Fleming’s mould. “New Non-Toxic Drug Said to Be the Most Powerful Germ Killer Ever”, read the New York Times on October 20th, 1940. Two years later a Connecticut woman named Anne Miller was on her deathbed with an untreatable streptococcal infection when she became the first person to receive an experimental penicillin injection. A day later she had made a miraculous recovery. Recognising its potential, the Allied governments quickly scaled up the production of penicillin as part of the war effort, and it was instrumental in saving the lives of those who might otherwise have died from infected wounds.

Although they were discovered relatively recently, antibiotics have existed in nature for billions of years – the evolutionary consequence of the microscopic battle that was raging long before humans existed. We are simply hijacking the weaponry of the microbial world. Some compounds, like penicillin, break down bacterial cell walls. Others, like tetracycline, which was isolated from a soil bacterium, prevent some bacteria from building critical proteins. In the four decades after penicillin was first mass-produced, pharmaceutical companies developed and sold approximately 120 antibiotics isolated from fungi, bacteria and other microbes.

X-ray crystallography versus antibiotic resistance
The early 20th century saw significant developments in X-ray crystallography, which now enables us to determine the fine atomic architecture of the protein targets of antibiotics, how antibiotics interact with these proteins and how better antibiotics may be designed.

Fleming, however, had concerns, and he voiced them during his Nobel Prize Lecture of 1945. “I would like to sound one note of warning,” he said. “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them and the same thing has occasionally happened in the body.”

Few heeded Fleming’s words. Doctors handed out antibiotics to treat everything from earaches to sinus infections – even though many of these were caused by viruses, not bacteria. When patients stopped taking the antibiotics before the infection was fully cleared, the hardy bacteria that survived could bounce back and spread their resistance to other bacteria. Moreover, the abuse of antibiotics was not limited to humans, as livestock owners realised the virtues of adding antibiotics to animal feed, preventing infections while also helping their animals put on weight quickly. Farmers were soon running an evolutionary experiment on an unprecedented scale. They weren’t just breeding animals; they were breeding superbugs.

A scientist synthesizes chemicals to tackle antibiotic resistance
The synthesis of complex chemicals enables pharmaceutical companies and academics to hunt for new starting points that may become antibiotics of the future.

Time and time again, the bacteria were beating the drugs. Penicillin was released in 1938; resistance appeared in 1945. Streptomycin was released in 1946; resistance appeared that same year. Tetracyclines were released in 1952; resistance had appeared two years earlier. The pharmaceutical industry, rather than keeping pace with its bacterial targets, has largely abandoned the field in favour of producing more profitable drugs for cancers. In the early 1980s, the US Food and Drug Administration was approving three new antibiotics per year. Today, that number is one every two years. In 2015, President Obama urged Congress to support a measure to spend $1.2 million addressing antibiotic-resistant bacteria, but it was never funded.

The scope of the challenge posed by antibiotic resistance to humanity is such that there is a call for a pact modelled after international climate change agreements. On 21st September 2016, the United Nations in New York held a high-level meeting to begin a process of global cooperation. “It is not that it may happen in the future,” Secretary-General Ban Ki-Moon warned. “It is a very present reality.” That day, all 193 UN member states signed a declaration agreeing to support an action plan to promote the responsible use of antibiotics and the development of new antibiotics, rapid diagnostic tests and surveillance measures for growing resistance. We will never now be rid of the dangers of superbugs but, as we face the threat of antibiotic resistance together, there is hope that we will be able to coexist with it, rather than being at the mercy of diseases we had once thought eradicated.

This is an excerpt from a 10-page feature in issue 4 of Avaunt, on newsstands now. Buy the current issue of Avaunt here.

Words: Brendan Borrell

Photography: Daniel Stier

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